Alcohol Induced Alterations to the Human Fecal VOC Metabolome

Studies have shown that excessive alcohol consumption impacts the intestinal microbiota composition, causing disruption of homeostasis (dysbiosis). However, this observed change is not indicative of the dysbiotic intestinal microbiota function that could result in the production of injurious and toxic products. Thus, knowledge of the effects of alcohol on the intestinal microbiota function and their metabolites is warranted, in order to better understand the role of the intestinal microbiota in alcohol associated organ failure. Here, we report the results of a differential metabolomic analysis comparing volatile organic compounds (VOC) detected in the stool of alcoholics and non-alcoholic healthy controls. We performed the analysis with fecal samples collected after passage as well as with samples collected directly from the sigmoid lumen. Regardless of the approach to fecal collection, we found a stool VOC metabolomic signature in alcoholics that is different from healthy controls. The most notable metabolite alterations in the alcoholic samples include: (1) an elevation in the oxidative stress biomarker tetradecane; (2) a decrease in five fatty alcohols with anti-oxidant property; (3) a decrease in the short chain fatty acids propionate and isobutyrate, important in maintaining intestinal epithelial cell health and barrier integrity; (4) a decrease in alcohol consumption natural suppressant caryophyllene; (5) a decrease in natural product and hepatic steatosis attenuator camphene; and (6) decreased dimethyl disulfide and dimethyl trisulfide, microbial products of decomposition. Our results showed that intestinal microbiota function is altered in alcoholics which might promote alcohol associated pathologies.     

Circadian Disorganization Alters Intestinal Microbiota

Intestinal dysbiosis and circadian rhythm disruption are associated with similar diseases including obesity, metabolic syndrome, and inflammatory bowel disease. Despite the overlap, the potential relationship between circadian disorganization and dysbiosis is unknown; thus, in the present study, a model of chronic circadian disruption was used to determine the impact on the intestinal microbiome. Male C57BL/6J mice underwent once weekly phase reversals of the light:dark cycle (i.e., circadian rhythm disrupted mice) to determine the impact of circadian rhythm disruption on the intestinal microbiome and were fed either standard chow or a high-fat, high-sugar diet to determine how diet influences circadian disruption-induced effects on the microbiome. Weekly phase reversals of the light:dark (LD) cycle did not alter the microbiome in mice fed standard chow; however, mice fed a high-fat, high-sugar diet in conjunction with phase shifts in the light:dark cycle had significantly altered microbiota. While it is yet to be established if some of the adverse effects associated with circadian disorganization in humans (e.g., shift workers, travelers moving across time zones, and in individuals with social jet lag) are mediated by dysbiosis, the current study demonstrates that circadian disorganization can impact the intestinal microbiota which may have implications for inflammatory diseases.     

How Self-Generated Thought Shapes Mood—The Relation between Mind-Wandering and Mood Depends on the Socio-Temporal Content of Thoughts

Recent work has highlighted that the generation of thoughts unrelated to the current environment may be both a cause and a consequence of unhappiness. The current study used lag analysis to examine whether the relationship between self-generated thought and negative affect depends on the content of the thoughts themselves. We found that the emotional content could strongly predict subsequent mood (e.g. negative thoughts were associated with subsequent negative mood). However, this direct relationship was modulated by the socio-temporal content of the thoughts: thoughts that were past- and other-related were associated with subsequent negative mood, even if current thought content was positive. By contrast, future- and self-related thoughts preceded improvements of mood, even when current thought content was negative. These results highlight the important link between self-generated thought and mood and suggest that the socio-temporal content plays an important role in determining whether an individual''s future affective state will be happy or sad.     

Inferring Patterns of Migration from Gene Frequencies under Equilibrium Conditions

A new maximum likelihood method to simultaneously estimate the parameters of any migration pattern from gene frequencies in stochastic equilibrium is developed, based on a model of multivariate genetic drift in a subdivided population. Motivated by simulations of this process in the simplified case of two subpopulations, problems related to the nuisance parameter q, the equilibrium gene frequency, are eliminated by conditioning on the observed mean gene frequency. The covariance matrix of this conditional distribution is calculated by constructing an abstract process that mimics the behavior of the original process in the subspace of interest. The approximation holds as long as there is limited differentiation between subpopulations. The bias and variance of estimates of long-range and short-range migration in a finite stepping stone model are evaluated by fitting the model to simulated data with known values of the parameters. Possible ecological extensions of the model are discussed.     

Age-specific optimal diets and optimal foraging tactics: A life-historic approach

By linking optimal foraging theory and optimal life history theory, we demonstrate that optimal diets, in general, may depend on the individual's age even when everything else remains the same. Older individuals (i.e., individuals with lower reproductive values) are predicted to have diets composed of highly nutritious food types that are possibly dangerous to pursue.     

Rapid and simple preparation of plasmids suitable for dideoxy DNA sequencing and other purposes.

Plasmid DNA released from bacteria by boiling in the presence of lysozyme and Triton x-100 and without further purification can be sequenced by the dideoxy method using T7 DNA polymerase, when conditions during alkali denaturation and subsequent ethanol precipitation are adjusted to remove contaminants. The samples remain in the same microcentrifuge tubes from the harvesting of the bacteria until the splitting of the sample into four aliquots for the termination reactions. Less background label is observed with end-labelled primers (radioactivity or fluorescence), but even when radioactive nucleotides are incorporated during the sequencing reactions, 250 bases or more can be read from template prepared from 1.5 ml bacterial culture. The DNA can also be cut by restriction enzymes; the purification procedure described thus provides the rapid preparation of plasmids for a variety of purposes.     

Sequence Characterization of a Unique Intergenic Spacer in Gadiformes Mitochondrial DNA

The nucleotide sequences of intergenic spacers located between the tRNA^Thr and tRNA^Pro genes in mitochondrial DNA of cod fishes (order Godiformes) were determined. Spacers from eight species representing two families of cod fishes were analyzed and found to vary in size from 25 to 99 bp. Each spacer sequence contains one or two copies of a conserved 17-bp motif. Four to five central nucleotides of this motif constitute a substitutional hot spot as observed from interspecific and intraspecific comparisons. The substitution rate of the spacer is approximately twice that of the variable part I of the mitochondrial DNA control region, making this sequence region interesting as a molecular marker in population studies or stock assessments of cod fishes. We propose that the spacer originated in a duplication event and evolved into a functional domain, perhaps by binding regulatory proteins. Accepted February 26, 1999